Interleukin-8 as an essential factor in the human chorionic gonadotropin-induced rabbit ovulatory process: interleukin-8 induces neutrophil accumulation and activation in ovulation.
The objective of our study was to elucidate the involvement of interleukin (IL)-8 in the hCG-induced rabbit ovulatory process. After administering hCG (100 IU i.v.), we examined myeloperoxidase (MPO) activity, which represents neutrophil accumulation; neutrophil elastase (NE) activity, which is an indicator of neutrophil activity; and levels of IL-8 in the ovaries. The maximal level of IL-8 was observed before MPO and NE activities reached a peak: production of IL-8, MPO, and NE activities peaked, respectively, at 4 h (5.58 +/- 0.88 pg/mg ovary, n = 13), 6 h (1.07 +/- 0.13 deltaA/min per gram ovary, n = 8), and 9 h (18.89 +/- 1.05 U/g ovary, n = 8). Anti-rabbit IL-8 antiserum given i.v. significantly reduced the maximal levels of hCG-induced MPO activity (antiserum vs. control; 0.34 +/- 0.04 vs. 1.12 +/- 0.11 deltaA/min per gram ovary, n = 14, p < 0.001) and NE activity (8.14 +/- 0.85 vs. 18.30 +/- 0.79 U/g ovary, n = 14, p < 0.001). The hCG-induced ovulation rate was significantly inhibited by the antiserum (50.5% vs. 83.9%, n = 14, p < 0.001). Intraperitoneal injection of 100 mg/kg of ONO-5046, a specific NE inhibitor, also attenuated the ovulation rate (ONO-5046 vs. vehicle; 56.0% vs. 74.0%, n = 14, p < 0.05). These findings clearly indicate that IL-8 has an important role in the hCG-induced ovulatory process through the accumulation and activation of neutrophils.
Ujioka
T
T
Department of Obstetrics and Gynecology, Kumamoto University School of Medicine, Japan.
Matsukawa
A
A
Tanaka
N
N
Matsuura
K
K
Yoshinaga
M
M
Okamura
H
H
D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000502:physiology*; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects; D010053:Ovary / Q000166:cytology* / Q000187:drug effects; D010060:Ovulation / Q000187:drug effects / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D006063:Chorionic Gonadotropin; D016209:Interleukin-8; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D009195:Peroxidase; D005998:Glycine